The main objective of this research proposal is to enhance our understanding of the cell survival-promoting activities of, with special emphasis on the central nervous system. The specific aims are as follows: 1) To determine if treatment of cultured cerebellar granule neurons with DNA damaging agents induces changes in the activity of NF-kB/Rel proteins. 2) To evaluate if NF-kB/Rel can modulate DNA damage-induced neuronal death. 3) To study the potential mechanisms of NF-kB/Rel- mediated neuronal protection against DNA damage-induced apoptosis. On a more general level, this proposal may aid in the understanding of programmed cell death and cellular response to DNA damage, which are directly related to cancer and chemo/radio-therapy. Furthermore, NF- kB/Rel has been demonstrated to be involved in a wide range of biological processes, including infection, inflammation, stress, proliferation, and differentiation. Exploration of the mechanisms of NF-kB/Rel activity and regulation will hopefully lead to a greater understanding of all of these processes.